Enhancing adoptive T-cell therapy with fucoidan-based IL-2 delivery microcapsules

Eun Young Jeon; Da-Som Choi; Seunghyun Choi; Ju-Young Won; Yunju Jo; Hye-Bin Kim; Youngmee Jung; Sang Chul Shin; Hophil Min; Hae Woong Choi; Myeong Sup Lee; Yoon Park; Justin J Chung; Hyung-Seung Jin

doi:10.1002/btm2.10362

Enhancing adoptive T-cell therapy with fucoidan-based IL-2 delivery microcapsules

Bioeng Transl Med. 2022 Jul 5;8(1):e10362. doi: 10.1002/btm2.10362. eCollection 2023 Jan.

Authors

Eun Young Jeon¹, Da-Som Choi², Seunghyun Choi^{3

4}, Ju-Young Won², Yunju Jo^{3

4}, Hye-Bin Kim², Youngmee Jung^{1

5

6}, Sang Chul Shin⁷, Hophil Min⁸, Hae Woong Choi⁴, Myeong Sup Lee⁹, Yoon Park³, Justin J Chung^{10

11}, Hyung-Seung Jin²

Affiliations

¹ Center for Biomaterials Biomedical Research Institute, Korea Institute of Science and Technology (KIST) Seoul South Korea.
² Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center University of Ulsan College of Medicine Seoul South Korea.
³ Theragnosis Center Biomedical Research Institute, Korea Institute of Science and Technology (KIST) Seoul South Korea.
⁴ Department of Life Sciences Korea University Seoul South Korea.
⁵ School of Electrical and Electronic Engineering Yonsei University Seoul South Korea.
⁶ Yonsei-KIST Convergence Research Institute Seoul South Korea.
⁷ Technology Support Center Korea Institute of Science and Technology (KIST) Seoul South Korea.
⁸ Doping Control Center Korea Institute of Science and Technology (KIST) Seoul South Korea.
⁹ Department of Biomedical Sciences University of Ulsan College of Medicine Seoul South Korea.
¹⁰ Transdisciplinary Department of Medicine and Advanced Technology Seoul National University Hospital Seoul South Korea.
¹¹ Department of Medicine Seoul National University College of Medicine Seoul South Korea.

Abstract

Adoptive cell therapy (ACT) with antigen-specific T cells is a promising treatment approach for solid cancers. Interleukin-2 (IL-2) has been utilized in boosting the efficacy of ACT. However, the clinical applications of IL-2 in combination with ACT is greatly limited by short exposure and high toxicities. Herein, a complex coacervate was designed to intratumorally deliver IL-2 in a sustained manner and protect against proteolysis. The complex coacervate consisted of fucoidan, a specific IL-2 binding glycosaminoglycan, and poly-l-lysine, a cationic counterpart (FPC²). IL-2-laden FPC² exhibited a preferential bioactivity in ex vivo expansion of CD8⁺T cells over Treg cells. Additionally, FPC² was embedded in pH modulating injectable gel (FPC²-IG) to endure the acidic tumor microenvironment. A single intratumoral administration of FPC²-IG-IL-2 increased expansion of tumor-infiltrating cytotoxic lymphocytes and reduced frequencies of myeloid populations. Notably, the activation and persistency of tumor-reactive T cells were observed only in the tumor site, not in the spleen, confirming a localized effect of FPC²-IG-IL-2. The immune-favorable tumor microenvironment induced by FPC²-IG-IL-2 enabled adoptively transferred TCR-engineered T cells to effectively eradicate tumors. FPC²-IG delivery system is a promising strategy for T-cell-based immunotherapies.

Keywords: adoptive T‐cell therapy; complex coacervate; fucoidan; immunotherapy; interleukin‐2.